GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition
Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherap...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1066 |
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| author | Jessica D. Hathaway-Schrader Duncan Norton Katherine Hastings Bently P. Doonan Shaun Tompkins Fritz Jennifer R. Bethard Janice S. Blum Azizul Haque |
| author_facet | Jessica D. Hathaway-Schrader Duncan Norton Katherine Hastings Bently P. Doonan Shaun Tompkins Fritz Jennifer R. Bethard Janice S. Blum Azizul Haque |
| author_sort | Jessica D. Hathaway-Schrader |
| collection | DOAJ |
| description | Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival. Several melanoma antigens (Ags) proposed as targets for immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which contain both human leukocyte antigen (HLA) class I and class II-restricted epitopes necessary for immune recognition. We have previously shown that an enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly expressed in professional Ag presenting cells (APCs), but absent or expressed at greatly reduced levels in many human melanomas. In the current study, we report that increased GILT expression generates a greater pool of antigenic peptides in melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the induction of GILT in human melanoma cells could aid in the development of a novel whole-cell vaccine for the enhancement of immune recognition of metastatic melanoma. |
| first_indexed | 2024-03-09T23:50:50Z |
| format | Article |
| id | doaj.art-933b8bee8101421f8223fc3fd557aa25 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:50:50Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-933b8bee8101421f8223fc3fd557aa252023-11-23T16:34:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233106610.3390/ijms23031066GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune RecognitionJessica D. Hathaway-Schrader0Duncan Norton1Katherine Hastings2Bently P. Doonan3Shaun Tompkins Fritz4Jennifer R. Bethard5Janice S. Blum6Azizul Haque7Department of Microbiology and Immunology, Hollings Cancer Center, Children’s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USADepartment of Microbiology and Immunology, Hollings Cancer Center, Children’s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USADepartment of Microbiology and Immunology, Hollings Cancer Center, Children’s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USADepartment of Microbiology and Immunology, Hollings Cancer Center, Children’s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USADepartment of Microbiology and Immunology, Hollings Cancer Center, Children’s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USADepartment of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USADepartment of Microbiology and Immunology, School of Medicine, Indiana University, Indianapolis, IN 46202, USADepartment of Microbiology and Immunology, Hollings Cancer Center, Children’s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USAMelanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival. Several melanoma antigens (Ags) proposed as targets for immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which contain both human leukocyte antigen (HLA) class I and class II-restricted epitopes necessary for immune recognition. We have previously shown that an enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly expressed in professional Ag presenting cells (APCs), but absent or expressed at greatly reduced levels in many human melanomas. In the current study, we report that increased GILT expression generates a greater pool of antigenic peptides in melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the induction of GILT in human melanoma cells could aid in the development of a novel whole-cell vaccine for the enhancement of immune recognition of metastatic melanoma.https://www.mdpi.com/1422-0067/23/3/1066gamma-IFN-inducible lysosomal thiol-reductase (GILT)melanomaAg presenting cells (APCs)human leukocyte antigen (HLA) class IIcathepsinsCD4+ T cells |
| spellingShingle | Jessica D. Hathaway-Schrader Duncan Norton Katherine Hastings Bently P. Doonan Shaun Tompkins Fritz Jennifer R. Bethard Janice S. Blum Azizul Haque GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition International Journal of Molecular Sciences gamma-IFN-inducible lysosomal thiol-reductase (GILT) melanoma Ag presenting cells (APCs) human leukocyte antigen (HLA) class II cathepsins CD4+ T cells |
| title | GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition |
| title_full | GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition |
| title_fullStr | GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition |
| title_full_unstemmed | GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition |
| title_short | GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition |
| title_sort | gilt expression in human melanoma cells enhances generation of antigenic peptides for hla class ii mediated immune recognition |
| topic | gamma-IFN-inducible lysosomal thiol-reductase (GILT) melanoma Ag presenting cells (APCs) human leukocyte antigen (HLA) class II cathepsins CD4+ T cells |
| url | https://www.mdpi.com/1422-0067/23/3/1066 |
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